J Korean Assoc Oral Maxillofac Surg.  2009 Apr;35(2):55-65.

Targeting Receptor Tyrosine Kinase on Endothelial Cells in an Orthotopic Tumor Model of Oral Squamous Cell Carcinorma

• Park YW
• Kim SH

Abstract

PURPOSE
We determined the therapeutic effects of blockade of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) receptor tyrosine kinases on the growth of oral squamous cell carcinoma (OSCC) xenografted in athymic nude mice. Experimental Design: We investigated the in vivo antitumor effects of a tyrosine kinase inhibitor for EGFR and VEGFR-2, AEE788 in a mouth floor (orthotopic) tumor model. Nude mice with orthotopic tumors were randomized to receive AEE788, paclitaxel, a combination of AEE788 and paclitaxel, or control. Antitumor mechanisms of AEE788 were determined by immunohistochemical/immunofluorescent and apoptosis assays.
RESULTS
Tumors of mice treated with AEE788 demonstrated down-regulation of phosphorylated EGFR, phosphorylated VEGFR and their downstream mediators (pMAPK and pAkt), decreased proliferative index, decreased microvessel density (MVD). As a result, growth of the primary tumor and nodal metastatic potentials were inhibited by AEE788.
CONCLUSION
These data show that EGFR and VEGFR can be molecular targets for the treatment of OSCC.

Keyword

Oral squamous cell carcinoma; Epidermal growth factor receptor; Vascular endothelial growth factor receptor; Nodal metastatic potential

MeSH Terms

Animals
Apoptosis
Carcinoma, Squamous Cell
Down-Regulation
Endothelial Cells
Epidermal Growth Factor
Mice
Mice, Nude
Microvessels
Mouth Floor
Paclitaxel
Phosphotransferases
Protein-Tyrosine Kinases
Purines
Receptor, Epidermal Growth Factor
Receptors, Vascular Endothelial Growth Factor
Transplantation, Heterologous
Tyrosine
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-2
Epidermal Growth Factor
Paclitaxel
Phosphotransferases
Protein-Tyrosine Kinases
Purines
Receptor, Epidermal Growth Factor
Receptors, Vascular Endothelial Growth Factor
Tyrosine
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-2